Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice

Kosaki, Naoto; Takaishi, Hironari; Kamekura, Satoru; Kimura, Tokuhiro; Okada, Yasunori; Li, Minqi; Amizuka, Norio; Chung, Ung Il; Nakamura, Kozo; Kawaguchi, Hiroshi; Toyama, Yoshiaki; DʼArmiento, Jeanine

doi:10.1016/j.bbrc.2006.12.234

Cited by 99 publications

(91 citation statements)

References 18 publications

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“…However, based on these results, we cannot deduce whether CD200-Fc acts directly on cells in the joint, causing them to reduce their output of TNF␣ and IL-1␤, or whether the fusion protein reduces the infiltration of inflammatory cells into the joint. MMP-13 mRNA levels were also reduced, which is consistent with the reduced degree of joint erosion in CD200-Fc-treated mice because MMP-13 is known to play a major role in bone and cartilage breakdown by enhancing the cleavage of type II collagen (14).…”

Section: Discussionsupporting

confidence: 75%

CD200‐FC, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen‐induced arthritis

Šimelyte

Criado

Essex

et al. 2008

Arthritis & Rheumatism

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Objective. The CD200 receptor (CD200R) is an inhibitory receptor expressed by myeloid cells that is postulated to play an important role in regulation of the immune system. The purpose of this study was to evaluate the efficacy of a soluble ligand of CD200R in established collagen-induced arthritis (CIA) in mice and to analyze changes in cytokine expression following therapy in order to understand its primary mechanism of action.Methods. Arthritis was induced in DBA/1 mice, and CD200-Fc fusion protein, an isotype control monoclonal antibody, or TNFR-Fc fusion protein was administered over a period of 10 days (total of 4 doses). Cytokine expression in the joint was assessed by flow cytometry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction.Results. CD200-Fc significantly reduced the severity of established arthritis at the clinical and histologic levels. The therapeutic effect of CD200-Fc at 1 mg/kg was comparable with that of TNFR-Fc at 4 mg/kg. CD200R was found to be expressed in arthritic synovia and in lymph nodes, yet no changes in T cell cytokine levels (interferon-␥, interleukin-5 [IL-5], IL-10, IL-17) were detected after CD200-Fc therapy. There was no evidence of an expansion of forkhead box P3-positive regulatory T cells or a change in serum anticollagen IgG1 and IgG2a levels. However, administration of CD200-Fc markedly decreased the expression of messenger RNA for tumor necrosis factor ␣, IL-1␤, IL-10, and matrix metalloproteinase 13 in the joint to the same extent as administration of TNFR-Fc.Conclusion. CD200-Fc is an effective therapeutic agent in established CIA that targets proinflammatory cytokine expression in the joint without any obvious systemic immunosuppressive effects. Our findings indicate that CD200-Fc has considerable potential as a novel therapeutic agent in rheumatoid arthritis in humans.

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Section: Discussionsupporting

confidence: 75%

CD200‐FC, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen‐induced arthritis

Šimelyte

Criado

Essex

et al. 2008

Arthritis & Rheumatism

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“…Interestingly, the remaining callus consisted of mineralized and vascularized cartilage 55 that was mechanically sound. 57 MMPs, 55 particularly MMP-9 54 and MMP-13, 58 have been implicated as important molecular mediators of soft-tohard callus transition. In vitro data support the fact that macrophages can efficiently produce MMPs and degrade the cartilage matrix, 59,60 with MMP production being a forte of M1 macrophages.…”

Section: Macrophage Participation In Hard Callus Formation and Remodementioning

confidence: 99%

Unraveling macrophage contributions to bone repair

et al. 2013

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Macrophages have reemerged to prominence with widened understanding of their pleiotropic contributions to many biologies and pathologies. This includes clear advances in revealing their importance in wound healing. Here we have focused on the current state of knowledge with respect to bone repair, which has received relatively little scientific attention compared with its soft-tissue counterparts. Our detailed characterization of resident tissue macrophages residing in bone-lining tissues (osteomacs), including their pro-anabolic function, exposed a more prominent role for these cells in bone biology than previously anticipated. Recent studies have confirmed the importance of macrophages in early inflammatory processes that establish the healing cascade after bone fracture. Emerging data support that macrophage influence extends into both anabolic and catabolic phases of repair, suggesting that these cells have prolonged and diverse functions during fracture healing. More research is needed to clarify macrophage phase-specific contributions, temporospatial subpopulation variance and macrophage specific-molecular mediators. There is also clear motivation for determining whether macrophage alterations underlie compromised fracture healing. Overall, there is strong justification to pursue strategies targeting macrophages and/or their products for improving normal bone healing and overcoming failed repair.

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“…Without regulation, active MMPs can cause extensive ECM remodeling and result in a spectrum of pathological conditions, including arthritis, cancer, atherosclerosis, and fibrosis (21,24,27). However, the absence of MMP activity results in unresolved repair in bone (16), stalled development (14), and impaired wound healing (reviewed in Ref. 11).…”

mentioning

confidence: 99%

Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration

Lei

Leong

Smith

et al. 2013

American Journal of Physiology-Cell Physiology

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Lei H, Leong D, Smith LR, Barton ER. Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration. Am J Physiol Cell Physiol 305: C529-C538, 2013. First published June 12, 2013 doi:10.1152/ajpcell.00051.2013.-Efficient skeletal muscle repair and regeneration require coordinated remodeling of the extracellular matrix (ECM). Previous reports have indicated that matrix metalloproteinases (MMPs) play the pivotal role in ECM remodeling during muscle regeneration. The goal of the current study was to determine if the interstitial collagenase MMP-13 was involved in the muscle repair process. Using intramuscular cardiotoxin injections to induce acute muscle injury, we found that MMP-13 expression and activity transiently increased during the regeneration process. In addition, in muscles from mdx mice, which exhibit chronic injury, MMP-13 expression and protein levels were elevated. In differentiating C2C12 cells, a murine myoblast cell line, Mmp13 expression was most pronounced after myoblast fusion and during myotube formation. Using pharmacological inhibition of MMP-13 to test whether MMP-13 activity is necessary for the proliferation, differentiation, migration, and fusion of C2C12 cells, we found a dramatic blockade of myoblast migration, as well as a delay in differentiation. In contrast, C2C12 cells with stable overexpression of MMP-13 showed enhanced migration, without affecting myoblast maturation. Taken together, these results support a primary role for MMP-13 in myoblast migration that leads to secondary effects on differentiation.collagenase; matrix metalloproteinase; muscle repair; myoblast maturation

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Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice

Cited by 99 publications

References 18 publications

CD200‐FC, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen‐induced arthritis

CD200‐FC, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen‐induced arthritis

Unraveling macrophage contributions to bone repair

Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration

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